context: 2 components of triglycerides break down
glycerol's fate
glycerol --> pyruvic acid (PA) --> acetyl-CoA --> goes into TCA cycle --> make NADH and FADH2
context: 2 components of triglycerides break down
3 fatty acids' fate
3 fatty acids --(beta-oxidation)--> acetyl-CoA --> enters TCA cycle --> lots of ATP
2 types of energy sources
1. lipids
2. carbohydrates
context: 2 types of energy sources
lipids
18 carbon fatty acid = net 144 ATP molecules
compact storage = hard to access = cannot produce ATP quickly (slow)
used in absence of glucose
context: 2 types of energy sources
carbohydrates
3 * 6 carbon sugars = net 108 ATP molecules
less compact storage = easy to access = can produce ATP quickly
use preferentially
lipogenesis
lipid synthesis (creating)
glycerol (dihydroxyacetone phosphate) + fatty acids (acetyl-CoA from lipids, amino acids, and carbohydrates) = triglycerides
T/F
you can break down anything and you can synthesize everything
FALSE. you CAN'T synthesize everything.
ex: essential fatty acids required for prostaglandin synthesis and cell membranes must be acquired through diet (plant-based fatty acid)
2 ways to get cholesterol
1. synthesis
2. dietary
context: 2 ways to get cholesterol
synthesis
endogenous - 1.0 g/day
1. liver: HMG-CoA reductase (rate-limiting step)
2. bile: 95% of bile reabsorbed
3. HDL: scavenged from blood stream
context: 2 ways to get cholesterol
dietary
exogenous - 0.5 g/day
1. meat, eggs, dairy
2. 80% of serum cholesterol
3. high saturated fats --> into elevated serum cholesterol
context: lipid transport
free fatty acids
easily diffuse across membranes because they are lipophilic
bound to albumin in blood
utilized for energy in glucose starved cells
context: lipid transport
lipoproteins
large lipid-protein complexes that houses triglycerides and cholesterol that insoluble (aggregate)
cannot diffuse across membranes due to large size
context: lipid transport
If triglycerides and cholesterol aggregate and are insoluble how do they get into the cell?
composition of lipoproteins:
1. surface (hydrophilic) due to:
a) phospholipids (PL)
b) apoproteins (APO)
-increase solubility of lipids in circulation
-determine cellular destination of lipids based on protein
-stimulate or inhibit enzymes involved in lipid metabolism
2. inside (hydrophobic)
a) triglycerides (TG) and cholesterol (Chol)
b) fat soluble vitamins
how are lipoproteins classified (2)?
based on shape and lipid:protein ratio
5 types of lipoproteins
1. chylomicrons - largest
2. very low density lipoproteins (VLDL)
3. intermediate density lipoproteins (IDL)
4. low density lipoproteins (LDL)
5. high density lipoproteins (HDL) - smallest
*densities of lipoproteins depend on their relative amounts of protein and lipids
context: 5 types of lipoproteins
chylomicrons
composition:
90% triglycerides, 4% cholesterol, 5% phospholipids, 1% protein
origin:
produced by intestinal epithelial cells (enterocytes)
function:
carry absorbed lipids from GI tract (ditet) into the blood stream via lymph capillaries (lacteals)
context: 5 types of lipoproteins
process of chylomicron production
dietary lipids (fatty acids and cholesterol absorbed through the brush border of the small intestines) + pancreatic lipase + bile salts --> in the endoplasmic reticulum of intestinal epithelial cells, lipid products (lipoproteins, cholesterol, triglycerides) are assembled into chylomicrons --> enter lacteal ("milky") --(lipoprotein lipase) --> breakdown of chylomicrons --> TGs to muscles and adipose tissue; cholesterol to liver
lipoprotein lipase (LPL)
enzyme on capillary epithelium in adipose, muscle, or liver tissue
process:
apoproteins (APO) on chylomicron surface --> allows correct delivery of chylomicron to tissue and lipase activation --> lipase turns triglycerides to glycerol and fatty acids --> glycerol and fatty acids enter cell for use; chylomicron remnant (CR) which is primarily cholesterol travels to hepatocytes (liver)
context: 5 types of lipoproteins
very low density lipoproteins (VLDL)
-triglycerides synthesized by liver and from conversion of excess carbohydrates
-cholesterol synthesized by liver and from degraded chylomicron remnants
function:
primary source of triglycerides for the body and transport the lipids (mainly TG) from the liver to the tissues
context: 5 types of lipoproteins
process of very low density lipoproteins (VLDL)
released into circulation --> (1) apoproteins on the surface target the VLDLs to muscle and adipose tissue (2) activate lipoprotein lipase in capillary walls to remove triglycerides from VLDL --> VLDL remnants/intermediate density lipoprotein (IDL)
context: 5 types of lipoproteins
intermediate density lipoproteins (IDL)
transport lipids from blood stream to the liver and circulation
context: 5 types of lipoproteins
process of intermediate density lipoproteins (IDL)
transported from bloodstream --> (1) ~50% of IDL converted to LDL by lipoprotein lipase removing TGs, (2) ~50% binds to LDL receptor on liver via apoproteins which then enters cell via receptor mediated endocytosis --> (a) removal of TGs = degraded into LDLs, (b) addition of TGs = recycled into VLDLs --> both released into circulation
context: 5 types of lipoproteins
low density lipoproteins (LDL)
main carrier of endogenous cholesterol from liver to tissues
context: 5 types of lipoproteins
process of low density lipoproteins (LDL)
circulation -->
(1) 75% LDL binds to LDL receptors in the liver via apoprotein (specific) --> receptor mediated endocytosis --> degraded (components recycled/consumed), (2) 24% bind to LDL receptors in the peripherals --> degraded/consumed for cell metabolism and maintenance --> excess cholesterol diffuses out of cells to INC. serum (blood) cholesterol, (3) 1% becomes oxidized --> enters endothelium of blood vessels --> start of atherosclerosis which is "bad"
context: 5 types of lipoproteins
high density lipoproteins (HDL)
self assemble in the plasma from (a) free cholesterol (lecithin-cholesterol acyl transferase [LCAT] esterifies free cholesterol, (b) lipoprotein fragments
function:
transports cholesterol from tissues to liver ("good" as a scavenger)
context: 5 types of lipoproteins
process of high density lipoproteins (HDL)
apoprotein specific, receptor-mediated endocytosis in the liver --> cholesterol is (a) consumed (into cell membrane or make LDLs) or (b) excreted in the bile --> HDLs released back into blood stream
9 steps in the distribution of lipoproteins by liver
1. liver cells synthesize VLDLs for discharge into the bloodstream
2. in peripheral capillaries, lipoprotein lipase removes many of the triglycerides from VLDLs, leaving IDLs; the triglycerides are broken down into fatty acids and monoglycerides
3. when IDLs reach the liver, additional triglycerides are removed, and the protein content of the lipoprotein is altered. This process creates LDLs, which are transported to peripheral tissues to deliver cholesterol.
4. LDLs leave the bloodstream through capillary pores or cross the endothelium by vesicular transport
5. once in the peripheral tissues, the LDLs are absorbed by means of receptor-mediated endocytosis. The amino acids and cholesterol then enter the cytoplasm
6. the cholesterol not used by the cell (in the synthesis of lipid membranes or other products) diffuses out of the cell
7. the cholesterol then reenters the bloodstream, where it is absorbed by HDLs and returned to the liver
8. in the liver, the HDLs are absorbed and their cholesterol is extracted. Some of the cholesterol that is recovered is used in the synthesis of LDLs; the rest is excreted in bile salts
9. the HDLs stripped of their cholesterol are released into the bloodstream to travel into peripheral tissues and absorb additional cholesterol
8 steps for regulations of cholesterol synthesis
1. LDL and IDL bind to LDL receptor (-R)
2. LDL-R cluster in clathrin coated pits on cell membrane
3. LDL-R vesicles pinch off and internalized = coated vesicles --> clathrin shed and recycled, LDL-R recycled
4. endosome fuses with lysosome
5. LDL disassembled into amino acids (apoproteins), cholesterol and triglycerides which is used for metabolism and maintenance of the cell
6. cholesterol esterified by acyl-CoA cholesterol acyltransferase (ACAT)
7. cholesterol stored in the endoplasmic reticulum (ER)